1. Field of the Invention
The invention relates to new acid-labile acetal glycosides of aldophosphamide and other cytocidal aldehydes as acetal components, a process for their preparation and their use as highly selective cytostatics in cancer therapy.
2. Background Information
It is known that malignant cells show elevated glycolysis and lactate production compared to normal tissue and the pH in the tumor tissue can be lowered by intravenously administered glucose (compare S. Tanneberger, Experimentelle und klinische Tumorchemotherapie; Allgemeine Tumorchemotherapie (Experimental and Clinical Tumour Chemotherapy; General Tumour Chemotherapy); G. Fischer Verlag, Stuttgart/New York 1980; Naturwiss., 46, 2 (1959); Cancer Res., 42, 1498 (1982); 42, 1505 (1982)).
In the past, it has been attempted to use these differences in pH between normal and tumor tissue for selective tumor therapy (compare Liebigs Ann. Chem., 1987, 847-856; Tetrahedron Lett., 22 (1981) 239-242). It has been sought to convert alkylating compounds, which on account of too low a differentiation between healthy and malignant tissue, show a very low therapeutic breadth, into non-toxic, acid-labile prodrug forms which are only selectively cleaved in the tumor tissue to active, alkylating cytostatics for reasons of the low pH prevailing there. In this manner, it was intended to seek a selective tumor therapy.
However, it has been shown that the compounds prepared in the abovementioned references did not prove so acid-labile that they were selectively cleaved back to the active cytocidal agents in the tumor tissue.